Project Summary Cryptosporidiosis is a diarrheal disease that disproportionately affects children and immunocompromised adults. The WHO estimates that in 2010, diarrheal disease accounted for 10.5% of deaths in children; of the known diarrheal diseases, cryptosporidiosis appears to one of the most deadly. Cryptosporidiosis was found second only to rotavirus in attributed cases of moderate-to- severe diarrhea in a multicenter epidemiology study across Africa and Southeast Asia. There are no efficacious drugs, no vaccines in development, and fundamental research on the Cryptosporidium parasite is sorely lacking. The MEDLE and SKSR gene families of Cryptosporidium are subtelomeric, polymorphic, and posses conserved protein motifs that are well known transport signals in the closely related intracellular parasites Plasmodium and Toxoplasma. These `PEXEL-like motifs' direct proteins to be transported out of the parasite and into the infected host cell, where they can remodel the cell and cut off the host immune response. This project aims to understand the function of the MEDLE and SKSR protein families and their role in Cryptosporidium pathogenesis.